Self-medicated. A new study suggests that some people suffer from excessive sleepiness due to a naturally occurring compound that acts like a sedative.

Credit: Digital Vision/Thinkstock

Hitting the wall in the middle of a busy work day is nothing unusual, and a caffeine jolt is all it takes to snap most of us back into action. But people with certain sleep disorders battle a powerful urge to doze throughout the day, even after sleeping 10 hours or more at night. For them, caffeine doesn't touch the problem, and more potent prescription stimulants aren't much better. Now, a study with a small group of patients suggests that their condition may have a surprising source: a naturally occurring compound that works on the brain much like the key ingredients in chill pills such as Valium and Xanax.

The condition is known as primary hypersomnia, and it differs from the better known sleep disorder narcolepsy in that patients tend to have more persistent daytime sleepiness instead of sudden "sleep attacks." The unknown cause and lack of treatment for primary hypersomnia has long frustrated David Rye, a neurologist at Emory University in Atlanta. "A third of our patients are on disability," he says, "and these are 20- and 30-year-old people."

Rye and colleagues began the new study with a hunch about what was going on. Several drugs used to treat insomnia promote sleep by targeting receptors for GABA, a neurotransmitter that dampens neural activity. Rye hypothesized that his hypersomnia patients might have some unknown compound in their brains that does something similar, enhancing the activity of so-called GABAA receptors. To try to find this mystery compound, he and his colleagues performed spinal taps on 32 hypersomnia patients and collected cerebrospinal fluid (CSF), the liquid that bathes and insulates the brain and spinal cord. Then they added the patients' CSF to cells genetically engineered to produce GABAA receptors, and looked for tiny electric currents that would indicate that the receptors had been activated.

In that first pass, nothing happened. However, when the researchers added the CSF and a bit of GABA to the cells, they saw an electrical response that was nearly twice as big as that caused by GABA alone. All of this suggests that the patients' CSF doesn't activate GABAA receptors directly, but it does make the receptors almost twice as sensitive to GABA, the researchers report today in Science Translational Medicine. This effect is similar to that of drugs called benzodiazepines, the active ingredients in antianxiety drugs such as Valium. It did not occur when the researchers treated the cells with CSF from people with normal sleep patterns.

Follow-up experiments suggested that the soporific compound in the patients' CSF is a peptide or small protein, presumably made by the brain, but otherwise its identity remains a mystery.

The idea that endogenous benzodiazepinelike compounds could cause hypersomnia was proposed in the early 1990s by Elio Lugaresi, a pioneering Italian sleep clinician, says Clifford Saper, a neuroscientist at Harvard Medical School in Boston. But several of Lugaresi's patients later turned out to be taking benzodiazepines, which undermined his argument, and the idea fell out of favor. Saper says the new work makes a "pretty strong case."

Based on these results, Rye and his colleagues designed a pilot study with seven patients using a drug called flumazenil, which counteracts benzodiazepines and is often used to treat people who overdose on those drugs. After an injection of flumazenil, the patients improved to near-normal levels on several measures of alertness and vigilance, the researchers report. Rye says these effects lasted up to a couple hours.

In hopes of longer-lasting benefits, the researchers persuaded the pharmaceutical company Hoffmann-La Roche, which makes the drug, to donate a powdered form that can be incorporated into dissolvable tablets taken under the tongue and a cream applied to the skin. One 30-something patient has been taking these formulations for 4 years and has improved dramatically, the researchers report in the paper. She has resumed her career as an attorney, from which her hypersomnia had forced her to take a leave of absence.

The findings are "certainly provocative," Saper says, although they'll have to be replicated in a larger, double-blind trial to be truly convincing.

Even so, says Phyllis Zee, a neurologist at Northwestern University in Evanston, Illinois: "This gives us a new window into thinking about treatments" for primary hypersomnia. "These patients don't respond well to stimulants," Zee says, so a better strategy may be to inhibit the sleep-promoting effects of GABA—or as Rye puts it, releasing the parking brake instead of pressing the accelerator.

The next steps are clear, Rye says: Identify the mystery compound, figure out a faster way to detect it, and conduct a larger clinical trial to test the benefits of flumazenil. However, the researchers first need someone to fund such a study. So far, Rye says, they've gotten no takers.

Computer programming in his dreams. I can’t even get something in a dream to stay constant from one “look” to the next. Occasionally when very intensely involved with a project I get prolonged dreams about generalities and that’s about it.

21
posted on 11/25/2012 5:32:46 PM PST
by HiTech RedNeck
(How long before all this "fairness" kills everybody, even the poor it was supposed to help???)

I composed most of my college papers in my head and whipped out 5 to 10 pages as quickly as the old Selectric would tolerate. The same behavior continues over 30 years as a software developer. The whole solution is cooked and dependent on my typing speed to come out in the real world. When working with customers on a problem, I have to be careful not to solve the problem before the customer has fully explained it.

The dream connection is more interesting. I have some dreams that go "on hold" in the morning and resume during the night. Most of it is in 3D and color. Who needs a TV with that going on :-) GABA interferes with that experience by tossing in noise and distractions. It was a harmless investigation to be avoided in the future. The anomaly isn't something I need to have fixed.

This brain death thing looks like it sure has gotten sloppy. In the name of getting transplant organs, they’ve killed or “killed” many humans or “bodies” in conditions outwardly identical to those in which some degree of recovery to a recognized living state has occurred, if not also recovery to lucidity. We trusted doctors to be sane, humane, and moral. Instead too often it’s nod and wink, and Obamacare can only make it worse.

26
posted on 11/25/2012 11:14:25 PM PST
by HiTech RedNeck
(How long before all this "fairness" kills everybody, even the poor it was supposed to help???)

And, trying not to run ahead of the customer is only logical. You haven’t really solved the problem until you maximally understood what the problem IS. Knowing the right questions to ask helps a lot, of course.

27
posted on 11/25/2012 11:17:29 PM PST
by HiTech RedNeck
(How long before all this "fairness" kills everybody, even the poor it was supposed to help???)

It is based on the idea that the small part of the brain responsible for the internal dialogue is the same part of the brain responsible for attention in general, and that as more attention is needed, it takes priority over maintaining the internal dialogue.

It is difficult for the brain to provide the energy needed to even support attention, much less the internal dialogue, so we use lots of brain tricks to shut out data that might be considered extraneous, and thus conserve energy.

For example, when we look at a picture of a person, we do not try to focus our attention on the entire image, but only on a “darting point”, looking at a small part, then another small part, then another, using our short term memory to imagine the whole picture at once. Importantly, when we look at a picture of a human face, the most frequently looked at points are the eyes. Here is a scan of eye movements of the darting point.

So the trick of the technique is to create more and more demand on our attention, which deprives the internal dialogue of the energy it needs to function, so it is quieted. And the longer it can voluntarily be turned off, the greater our control over it becomes.

The technique involves walking. Just ordinary walking is not easy, and demands considerable attention directed towards the legs. The next part is as you are walking, to hold the fingers in some unusual way, it doesn’t matter how, as long as it is unusual enough to attract your attention to your arms as well. Your arms just hang normally as they do when you typically walk, so it’s just the fingers that are odd.

So now your attention is in two directions. But the third part is the real attention grabber. By unfocusing your eyes, you defeat the “darting point” of your visual focus, and instead, everything in a 180 degree view in front of you becomes of equal importance to your attention. Which consumes an enormous amount of attention.

It takes just a little practice to learn how to walk with unfocused eyes, either looking at the ground 10-15 feet in front of you, or over the horizon, but it is not terribly difficult to learn.

So there is the technique. Walking, holding your fingers in an unusual way or ways, and unfocusing your eyes. Not very hard at all.

A few personal observations about the technique:

Don’t carry physical objects in your hands, as it can get annoying. I dislike even wearing a wristwatch when doing this. Rings are right out.

Never listen to music while you are doing this, or you may get a ferocious “ear worm”, the song endlessly repeating in your head. But if you have an annoying “ear worm” on its own while doing this technique, it will totally burn itself out and won’t trouble you any longer. Yippee!, if such things annoy you.

You can do the technique day or night, as long or short a walk as you like, because the effects are generally cumulative. Some people stop after a couple of weeks because even though they are getting a better state of mental focus and unfocus, they dislike the feeling of silence, like some people dislike quiet, so bring a boom box with them when they go camping.

One thing that some people notice after doing this technique for a while is that they start to get unusual sensations. Typically we ignore or block the vast majority of sensory input available to us, and sustained silence is bound to let some sensations we previously ignored through. I’ve never quite understood why a few people find this so disturbing, but a few do. Most just think it is cool.

I eat a Zone Bar with my evening mix of pills to avoid both the empty stomach and the wake up from the blood sugar crash. That carries me a good 6 hours before a blood sugar crash wakes me. Ibuprofen or aspirin is necessary at bed time or the pain in my back makes sleeping impossible.

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